To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) ... more To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G. We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation. Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random-effects models among multigravidae showed that IPTp-SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was >10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47). There appears to be a prevalence of 581G above which IPTp-SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is >10.1% to define the specific prevalence threshold where new strategies should be deployed.
Tropical medicine & international health : TM & IH, 2015
To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) ... more To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G. We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation. Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.0...
Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodiu... more Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. SNP polymorphism in ...
PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocy... more PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This respon...
Journal of immunology (Baltimore, Md. : 1950), 1998
Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. I... more Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any...
The American journal of tropical medicine and hygiene, 1996
We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falcipa... more We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falciparum infections that were below the threshold of detection of blood film examination. This revealed a substantial group of asymptomatic, submicroscopically patent infections within the population of a Sudanese village present throughout the year although clinical malaria episodes were almost entirely confined to the transmission season. In our September, January, April, and June surveys, the PCR-detected prevalences were 13%, 19%, 24%, and 19%, respectively. These figures reveal a much higher prevalence of dry season infection than previous microscopic surveys have indicated. Furthermore, 20% of a cohort of 79 individuals were healthy throughout the September to November transmission season but were PCR-positive for P. falciparum in a least one of a series of samples taken in the ensuing months. Levels of exposure to P. falciparum infection were therefore higher than was previously believ...
The American journal of tropical medicine and hygiene, 2008
The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase... more The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine-pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather t...
To examine the association between travel (recency of travel, transmission intensity at destinati... more To examine the association between travel (recency of travel, transmission intensity at destination compared to origin and duration of travel) and confirmed malaria in Uganda. Health facility-based case-control study in highland (~2,200 m), and highland fringe (~1,500 m) areas with adjustment for other covariates. In the highland site, patients who had travelled to areas of higher transmission intensity than home areas recently were nearly 7 times more likely to have confirmed malaria than those who had not (OR 6.9; p=0.01, 95% CI: 1.4-33.1). In the highland fringe site, there was a statistically significant association between travel and malaria (OR 2.1; p=0.04, 95% CI: 1.1-3.9). For highland areas, health authorities need to consider migrants when designing malaria control programs. Control interventions should include information campaigns reminding residents in these areas of the risk of malaria infection through travel and to provide additional mosquito nets for migrants to use during travel. Health authorities may wish to improve diagnosis in health facilities in highland areas by adding travel history to malaria case definitions. Where routine monitoring data are used to evaluate the impact of interventions on the malaria burden in highland areas, health authorities and donors need ensure that only cases from the local area and not &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;imported cases&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; are counted. This article is protected by copyright. All rights reserved.
Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent preventive treatment (I... more Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent preventive treatment (IPT) of malaria, but resistance threatens its efficacy. We found marked regional differences in the genotypes responsible for SP resistance when mapping recent surveys of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. In West Africa, a &amp;amp;amp;amp;amp;amp;#39;partially resistant&amp;amp;amp;amp;amp;amp;#39; combination of dhfr N51I, N59R, and S108N with dhps A437G predominates, whereas in East Africa the &amp;amp;amp;amp;amp;amp;#39;fully resistant&amp;amp;amp;amp;amp;amp;#39; combination of dhfr N51I, N59R, and S108N with dhps A437G+K540E is found. There are three East African foci where &amp;amp;amp;amp;amp;amp;#39;fully resistant&amp;amp;amp;amp;amp;amp;#39; populations have additionally acquired dhps 581G and/or dhfr 164L to become &amp;amp;amp;amp;amp;amp;#39;super resistant&amp;amp;amp;amp;amp;amp;#39;. SP-IPT in infants and pregnant women is reported to have failed in super resistant areas prompting review of SP-IPT use in affected areas.
Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recom... more Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recommended as an additional malaria control intervention in high transmission areas of sub-Saharan Africa, provided its protective efficacy is not compromised by SP resistance. A significant obstacle in implementing SP-IPTi, is in establishing the degree of resistance in an area. Since SP monotherapy is discontinued, no contemporary measures of in vivo efficacy can be made, so the World Health Organisation has recommended a cut-off based upon molecular markers, stating that SP-IPTi should not be implemented when the prevalence of the dhps 540E mutation among infections exceeds 50%. We created a geo-referenced database of SP resistance markers in Africa from published literature. By selecting surveys of malaria infected blood samples conducted since 2004 we have mapped the contemporary prevalence of dhps 540E. Additional maps are freely available in interactive form at http://www.drugresistancemaps.org/ipti/. Eight countries in East Africa are classified as unsuitable for SP-IPTi when data are considered at a national level. Fourteen countries in Central and West Africa were classified as suitable while seven countries had no available contemporary data to guide policy. There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi.
The declining efficacy of chloroquine and pyrimethamine/sulphadoxine in the treatment of human ma... more The declining efficacy of chloroquine and pyrimethamine/sulphadoxine in the treatment of human malaria has led to the use of newer antimalarials such as mefloquine and artemisinin. Sequence polymorphisms in the pfmdr1 gene, the gene encoding the plasmodial homologue of mammalian multidrug resistance transporters, have previously been linked to resistance to chloroquine in some, but not all, studies. In this study, we have used a genetic cross between the strains HB3 and 3D7 to study inheritance of sensitivity to the structurally unrelated drugs mefloquine and artemisinin, and to several other antimalarials. We find a complete allelic association between the HB3-like pfmdr1 allele and increased sensitivity to these drugs in the progeny. Different pfmdr1 sequence polymorphisms in other unrelated lines were also associated with increased sensitivity to these drugs. Our results indicate that the pfmdr1 gene is an important determinant of susceptibility to antimalarials, which has major implications for the future development of resistance.
To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) ... more To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G. We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation. Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01] and 581G was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random-effects models among multigravidae showed that IPTp-SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47). There appears to be a prevalence of 581G above which IPTp-SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10.1% to define the specific prevalence threshold where new strategies should be deployed.
Tropical medicine & international health : TM & IH, 2015
To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) ... more To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G. We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation. Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.0...
Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodiu... more Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. SNP polymorphism in ...
PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocy... more PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This respon...
Journal of immunology (Baltimore, Md. : 1950), 1998
Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. I... more Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any...
The American journal of tropical medicine and hygiene, 1996
We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falcipa... more We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falciparum infections that were below the threshold of detection of blood film examination. This revealed a substantial group of asymptomatic, submicroscopically patent infections within the population of a Sudanese village present throughout the year although clinical malaria episodes were almost entirely confined to the transmission season. In our September, January, April, and June surveys, the PCR-detected prevalences were 13%, 19%, 24%, and 19%, respectively. These figures reveal a much higher prevalence of dry season infection than previous microscopic surveys have indicated. Furthermore, 20% of a cohort of 79 individuals were healthy throughout the September to November transmission season but were PCR-positive for P. falciparum in a least one of a series of samples taken in the ensuing months. Levels of exposure to P. falciparum infection were therefore higher than was previously believ...
The American journal of tropical medicine and hygiene, 2008
The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase... more The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine-pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather t...
To examine the association between travel (recency of travel, transmission intensity at destinati... more To examine the association between travel (recency of travel, transmission intensity at destination compared to origin and duration of travel) and confirmed malaria in Uganda. Health facility-based case-control study in highland (~2,200 m), and highland fringe (~1,500 m) areas with adjustment for other covariates. In the highland site, patients who had travelled to areas of higher transmission intensity than home areas recently were nearly 7 times more likely to have confirmed malaria than those who had not (OR 6.9; p=0.01, 95% CI: 1.4-33.1). In the highland fringe site, there was a statistically significant association between travel and malaria (OR 2.1; p=0.04, 95% CI: 1.1-3.9). For highland areas, health authorities need to consider migrants when designing malaria control programs. Control interventions should include information campaigns reminding residents in these areas of the risk of malaria infection through travel and to provide additional mosquito nets for migrants to use during travel. Health authorities may wish to improve diagnosis in health facilities in highland areas by adding travel history to malaria case definitions. Where routine monitoring data are used to evaluate the impact of interventions on the malaria burden in highland areas, health authorities and donors need ensure that only cases from the local area and not &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;imported cases&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; are counted. This article is protected by copyright. All rights reserved.
Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent preventive treatment (I... more Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent preventive treatment (IPT) of malaria, but resistance threatens its efficacy. We found marked regional differences in the genotypes responsible for SP resistance when mapping recent surveys of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. In West Africa, a &amp;amp;amp;amp;amp;amp;#39;partially resistant&amp;amp;amp;amp;amp;amp;#39; combination of dhfr N51I, N59R, and S108N with dhps A437G predominates, whereas in East Africa the &amp;amp;amp;amp;amp;amp;#39;fully resistant&amp;amp;amp;amp;amp;amp;#39; combination of dhfr N51I, N59R, and S108N with dhps A437G+K540E is found. There are three East African foci where &amp;amp;amp;amp;amp;amp;#39;fully resistant&amp;amp;amp;amp;amp;amp;#39; populations have additionally acquired dhps 581G and/or dhfr 164L to become &amp;amp;amp;amp;amp;amp;#39;super resistant&amp;amp;amp;amp;amp;amp;#39;. SP-IPT in infants and pregnant women is reported to have failed in super resistant areas prompting review of SP-IPT use in affected areas.
Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recom... more Intermittent preventive treatment of infants (IPTi) with sulphadoxine pyrimethamine (SP) is recommended as an additional malaria control intervention in high transmission areas of sub-Saharan Africa, provided its protective efficacy is not compromised by SP resistance. A significant obstacle in implementing SP-IPTi, is in establishing the degree of resistance in an area. Since SP monotherapy is discontinued, no contemporary measures of in vivo efficacy can be made, so the World Health Organisation has recommended a cut-off based upon molecular markers, stating that SP-IPTi should not be implemented when the prevalence of the dhps 540E mutation among infections exceeds 50%. We created a geo-referenced database of SP resistance markers in Africa from published literature. By selecting surveys of malaria infected blood samples conducted since 2004 we have mapped the contemporary prevalence of dhps 540E. Additional maps are freely available in interactive form at http://www.drugresistancemaps.org/ipti/. Eight countries in East Africa are classified as unsuitable for SP-IPTi when data are considered at a national level. Fourteen countries in Central and West Africa were classified as suitable while seven countries had no available contemporary data to guide policy. There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi.
The declining efficacy of chloroquine and pyrimethamine/sulphadoxine in the treatment of human ma... more The declining efficacy of chloroquine and pyrimethamine/sulphadoxine in the treatment of human malaria has led to the use of newer antimalarials such as mefloquine and artemisinin. Sequence polymorphisms in the pfmdr1 gene, the gene encoding the plasmodial homologue of mammalian multidrug resistance transporters, have previously been linked to resistance to chloroquine in some, but not all, studies. In this study, we have used a genetic cross between the strains HB3 and 3D7 to study inheritance of sensitivity to the structurally unrelated drugs mefloquine and artemisinin, and to several other antimalarials. We find a complete allelic association between the HB3-like pfmdr1 allele and increased sensitivity to these drugs in the progeny. Different pfmdr1 sequence polymorphisms in other unrelated lines were also associated with increased sensitivity to these drugs. Our results indicate that the pfmdr1 gene is an important determinant of susceptibility to antimalarials, which has major implications for the future development of resistance.
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